Research has highlighted the prevalence and disruptiveness of fatigue, depression, and disruptions in sleep and physical activity (i.e., sickness behaviors) during chemotherapy. Biological mechanisms of sickness behaviors secondary to chemotherapy remain unknown, however. One potential biological mechanism of sickness behaviors is increased pro-inflammatory cytokines. Cross-sectional observational studies suggest that circulating pro-inflammatory cytokines are higher in post-treatment breast cancer survivors who experience chronic cancer-related fatigue. Despite these data, no studies have longitudinally examined the relationship between sickness behaviors and pro-inflammatory cytokines during and after chemotherapy. The trajectory and timing of pro-inflammatory cytokines relative to sickness behaviors is therefore unknown. Moreover, the components through which behavioral interventions exert beneficial effects on cytokines and sickness behaviors is unclear; one possibility is by increasing relaxed mood. The proposed project will assess fatigue, depression, sleep, activity, and circulating pro-inflammatory cytokines via self-report, actigraphy, and venipuncture in 150 gynecologic cancer patients receiving platinum- and taxane-based chemotherapy, one of the most arduous treatment regimens for cancer. Patients will be assessed the week before and the week after their first, third, and sixth chemotherapy infusions, as well as six and twelve months after chemotherapy ends. This study design will capture changes in sickness behaviors and cytokines on-treatment as well as in the early survivorship period. Patient participants who report clinically significant fatigue or depression a the twelve month assessment will participate in an experimental induction of relaxed mood to test the short-term effects of relaxation on cytokines and sickness behaviors. Because women without cancer also experience fatigue, depression, poor sleep, and reduced physical activity, and because data are sparse regarding normal fluctuations in circulating pro-inflammatory cytokines, the study will also assess sickness behaviors, and pro-inflammatory cytokines over a comparable time period in a sample of 150 women without cancer matched individually to patients based on age and zip code. The study will provide valuable information regarding the natural course of sickness behaviors and circulating pro-inflammatory cytokines in cancer patients treated with chemotherapy, including rates of change, temporal interrelationships, variation compared to women without cancer. In addition, it will determine whether induction of relaxation is an effective component of behavioral interventions to reduce sickness behaviors. These data will form the basis for future studies examining biobehavioral mechanisms of sickness behaviors and interventions to ameliorate them. PUBLIC HEALTH RELEVANCE: A better understanding of potential mechanisms underlying common symptoms during chemotherapy may be helpful in developing more effective interventions to prevent or reduce these symptoms, thereby improving public health. The proposed study will model change and relationships over time between fatigue, depression, disruptions in sleep and physical activity, and pro-inflammatory cytokines in gynecologic cancer patients during chemotherapy and early survivorship, and over a comparable period of time in a matched sample of women without cancer. To examine whether behavioral interventions improve symptoms and inflammation through relaxation, patient participants who report clinically significant fatigue or depression will be invited to participate in experimental induction of relaxd mood to determine short-term effects on cytokines and symptoms.